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13 pages, 1107 KB  
Article
Quantifying the Functional Gap in Alkaptonuria Through Machine Learning and Clinical Data Integration
by Anna Visibelli, Rebecca Finetti, Bianca Roncaglia, Alfonso Trezza, Barbara Marzocchi, Ottavia Spiga and Annalisa Santucci
Bioengineering 2026, 13(6), 604; https://doi.org/10.3390/bioengineering13060604 - 22 May 2026
Viewed by 317
Abstract
Alkaptonuria (AKU) is a rare inherited metabolic disorder characterized by progressive musculoskeletal damage, chronic pain, and functional heterogeneity. To better quantify this variability, we introduced the concept of the functional age gap, defined as the difference between chronological age and a data-derived estimate [...] Read more.
Alkaptonuria (AKU) is a rare inherited metabolic disorder characterized by progressive musculoskeletal damage, chronic pain, and functional heterogeneity. To better quantify this variability, we introduced the concept of the functional age gap, defined as the difference between chronological age and a data-derived estimate of functional age. The study included 134 patients with AKU from the ApreciseKUre database. Functional age was calculated by mapping Health Assessment Questionnaire Disability Index (HAQ-DI) and Knee Injury and Osteoarthritis Outcome Score (KOOS) values to age-referenced normative data. Most patients (94.8%) showed a positive functional age gap, with a mean difference of 15 years, which indicates a functionally older profile than expected for their chronological age. A bagging ensemble of decision trees was then used to explore relationships between clinical variables and functional age gap severity. The model achieved moderate but stable classification performance across repeated stratified cross-validation (64%), consistent with an exploratory analysis in a small rare-disease cohort. SHapley Additive exPlanations analysis identified age, AKUSSI spinal pain, AKUSSI joint pain, Schober test, and hip and knee activity as the most influential predictors. These findings support the functional age gap as an interpretable, hypothesis-generating descriptive metric for functional assessment in AKU, while its predictive utility for individual patient stratification will require validation in larger and longitudinal cohorts. Full article
(This article belongs to the Special Issue New Sights of Data Analysis and Digital Model in Biomedicine)
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15 pages, 269 KB  
Article
The Role of Central Sensitization and Emotional Comorbidities in Temporomandibular Involvement Among Patients with Psoriatic Arthritis
by José Antonio Blanco, Antonio Márquez, Esther Toledano, Rubén Queiro, Javier Martín-Vallejo, María José Fernández-Gómez, Carolina Chacón, Roberto Díaz-Peña, Daniel Martín, Cristina Hidalgo, María Dolores Sánchez, Moisés León González and Carlos Montilla
Life 2026, 16(4), 697; https://doi.org/10.3390/life16040697 - 21 Apr 2026
Viewed by 565
Abstract
Background: Temporomandibular disorders (TMDs) are frequently underdiagnosed in patients with psoriatic arthritis (PsA), and the mechanisms underlying their development remain poorly understood. While inflammatory processes may contribute, central pain sensitization and psychological factors could play a significant role in TMD pathogenesis. Objective: The [...] Read more.
Background: Temporomandibular disorders (TMDs) are frequently underdiagnosed in patients with psoriatic arthritis (PsA), and the mechanisms underlying their development remain poorly understood. While inflammatory processes may contribute, central pain sensitization and psychological factors could play a significant role in TMD pathogenesis. Objective: The objectives of this study were to evaluate clinical characteristics, disease activity, psychiatric comorbidities, and pain processing mechanisms in PsA patients with and without TMD and to identify factors independently associated with temporomandibular involvement. Methods: This cross-sectional observational study included 190 consecutive PsA patients (CASPAR criteria) from a single tertiary center. Patients with fibromyalgia were excluded. TMD was assessed by maxillofacial specialists. Disease activity (cDAPSA), functional status (HAQ-DI), disease impact (PsAID-12), central sensitization (Central Sensitization Inventory, CSI), kinesiophobia (Tampa Scale for Kinesiophobia, TSK-11), pressure pain threshold (algometry), and emotional comorbidities (Hospital Anxiety and Depression Scale, HADS) were evaluated. An exploratory binary logistic regression identified a factor independently associated with TMD. Results: Twenty-five patients (13.1%) had confirmed TMD, with a significant female predominance (76% vs. 39%; p = 0.001). Only 24% of patients exhibited structural damage on orthopantomography. TMD patients showed higher CSI scores (52 vs. 32; p < 0.001), greater kinesiophobia (TSK-11: 30 vs. 23; p = 0.002), lower pressure pain thresholds (2.1 vs 2.7 kg/cm2; p = 0.03), and higher anxiety (HADS-A: 9 vs. 5; p = 0.001) and depression scores (HADS-D: 6.5 vs. 3; p = 0.001). TMD patients also exhibited worse functional status (HAQ-DI: 0.7 vs. 0.3; p = 0.001) and greater disease impact (PsAID-12: 4.8 vs. 2.9; p = 0.001). In multivariate analysis, central sensitization (OR: 1.1; 95%CI: 1.04–1.18; p = 0.001) and anxiety (OR: 1.2; 95%CI: 1.02–1.61; p = 0.02) were independently associated with TMD (Nagelkerke R2 = 0.48). Conclusion: TMD in PsA is associated with central sensitization and anxiety rather than mechanisms secondary to bone damage. These findings support a multidimensional approach incorporating screening for central sensitization and psychiatric comorbidities in PsA patients with temporomandibular symptoms. Full article
15 pages, 516 KB  
Article
Obstructive Sleep Apnea in Psoriatic Arthritis: Clinical Characteristics and Comorbidities
by Miguel A. Hernández-Mezquita, Esther Toledano, Rubén Queiró, Javier Martín-Vallejo, María José Fernández-Gómez, Carolina Cristina Chacón, Roberto Díaz-Peña, Pilar Sánchez-Conde, Daniel Martín, Cristina Hidalgo, María Dolores Sánchez, Inés Llamas-Ramos, Erik Díaz and Carlos Montilla
Biomedicines 2026, 14(3), 491; https://doi.org/10.3390/biomedicines14030491 - 24 Feb 2026
Cited by 1 | Viewed by 962
Abstract
Background: Obstructive sleep apnea (OSA) is increasingly recognized in chronic inflammatory diseases, yet its prevalence and clinical correlates in psoriatic arthritis (PsA) remain poorly characterized. Objective: The objective of this study was to evaluate OSA prevalence and its relationship with disease [...] Read more.
Background: Obstructive sleep apnea (OSA) is increasingly recognized in chronic inflammatory diseases, yet its prevalence and clinical correlates in psoriatic arthritis (PsA) remain poorly characterized. Objective: The objective of this study was to evaluate OSA prevalence and its relationship with disease activity, functional impairment, and comorbidities in PsA patients. Methods: A cross-sectional analysis of 247 consecutive PsA patients was conducted. OSA diagnosis was determined through medical record review. Disease activity was assessed using cDAPSA and ASDAS-CRP. Functional disability was measured using HAQ-DI and BASFI. Sleep quality (PSQI) and psychological symptoms (HADS) were evaluated. Inflammatory markers included CRP, IL-6, and TNF-α. Multivariable logistic regression identified independent predictors of OSA. Results: OSA prevalence was found to be 8.9% (22/247). OSA+ patients had significantly higher median age (58.0 vs. 54.0 years, p = 0.02), tender joint count (2.0 vs. 1.0, p = 0.002), functional disability (1.1 vs. 0.3, p = 0.001), fatigue (30.5 vs. 38.0, p = 0.04), anxiety (7.5 vs. 5.0, p = 0.03), depression (7.0 vs. 3.0, p = 0.004), and worse sleep quality (11.5 vs. 7.0, p = 0.001). Notably, no significant differences in inflammatory markers (CRP, swollen joints) were found between groups despite substantially higher pain burden in OSA+ patients. Female sex and greater tender joint count emerged as independent predictors of OSA. Conclusions: OSA occurs in ~9% of unselected PsA patients and is independently associated with functional disability, psychological distress, and elevated tender joint counts despite comparable inflammatory markers. This dissociation suggests that OSA drives pain amplification through non-inflammatory mechanisms. These findings support the use of systematic OSA screening in PsA patients with pain or disability disproportionate to inflammatory burden, particularly in those with psychological comorbidities. Full article
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18 pages, 537 KB  
Article
Structural and Functional Outcomes in Rheumatoid Arthritis After 10-Year Therapy with Disease-Modifying Antirheumatic Drugs Under Tight Control: Evidence from Real-World Cohort Data
by Shunsuke Mori, Akitomo Okada, Toshimasa Shimizu, Ayuko Takatani and Tomohiro Koga
J. Clin. Med. 2025, 14(19), 6832; https://doi.org/10.3390/jcm14196832 - 26 Sep 2025
Cited by 1 | Viewed by 1799
Abstract
Objectives: To examine long-term outcomes and predictors of structural and functional remission in rheumatoid arthritis (RA) after 10-year disease-modifying antirheumatic drug (DMARD) therapy under tight control. Methods: We used real-world cohort data from RA patients who completed 10-year DMARD therapy toward [...] Read more.
Objectives: To examine long-term outcomes and predictors of structural and functional remission in rheumatoid arthritis (RA) after 10-year disease-modifying antirheumatic drug (DMARD) therapy under tight control. Methods: We used real-world cohort data from RA patients who completed 10-year DMARD therapy toward remission or low disease activity based on every-3-month measurements between April 2001 and July 2024. Baseline characteristics, disease control during follow-up, and outcomes after 10 years were examined. Results: Among 204 patients, 76% received biological and/or non-biological targeted DMARDs. Clinical remission, structural remission defined as an increase in modified total Sharp score (mTSS) ≤ 5 per 10 years, and functional remission defined as health assessment questionnaire-disability index (HAQ-DI) ≤ 0.5 were achieved by 68.1%, 73.0%, and 81.4% of patients, respectively. The mean increase (∆) in mTSS was 5.4 for 10 years (∆erosion score, 1.2; ∆joint space narrowing [JSN] score, 4.2), and 28.9% of patients had no structural progression (51% for erosion score and 34.8% for JSN score). Mean HAQ-DI was 0.26. During a 10-year follow-up, 8.8% of patients experienced high or moderate disease activity lasting for ≥12 months and they had a low structural remission rate (11.1%) and functional remission rate (16.6%). According to multivariable logistic regression analysis, baseline mTSS and JNS score (but not erosion score) were strong predictors for structural and functional remission after 10 years. Conclusions: Structural damage progression and functional loss are limited during 10-year tightly controlled DMARD therapy. Compared with bone erosion, JSN appears to be of much higher relevance to structural and functional outcomes. Full article
(This article belongs to the Special Issue Rheumatoid Arthritis: Clinical Updates on Diagnosis and Treatment)
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18 pages, 763 KB  
Article
Relationship Between High Serum Levels of Follistatin with Impaired Physical Function, and Severe Disease Activity in Rheumatoid Arthritis
by Fabiola Gonzalez-Ponce, Jorge Ivan Gamez-Nava, Heriberto Jacobo-Cuevas, Juan Manuel Ponce-Guarneros, Edgar Ricardo Valdivia-Tangarife, Cesar Arturo Nava-Valdivia, Norma Alejandra Rodriguez-Jimenez, Melissa Ramirez-Villafaña, Eli Efrain Gomez-Ramirez, Sergio Antonio Gonzalez-Vazquez, Aniel Jessica Leticia Brambila-Tapia, Eva Maria Olivas-Flores, Sylvia Totsuka-Sutto, Ernesto German Cardona-Muñoz and Laura Gonzalez-Lopez
Int. J. Mol. Sci. 2025, 26(17), 8232; https://doi.org/10.3390/ijms26178232 - 25 Aug 2025
Viewed by 1963
Abstract
Rheumatoid arthritis (RA) is a highly prevalent chronic inflammatory rheumatic disorder leading to functional impairment and sequels. The search for new biomarkers helping in detecting RA subjects of high risk of functional disability is required. Studies showing high follistatin levels in RA have [...] Read more.
Rheumatoid arthritis (RA) is a highly prevalent chronic inflammatory rheumatic disorder leading to functional impairment and sequels. The search for new biomarkers helping in detecting RA subjects of high risk of functional disability is required. Studies showing high follistatin levels in RA have been described; however, none of them have placed focus on the role of follistatin as marker of deteriorated functionality. We aim to identify whether follistatin concentrations could be a potential biomarker of physical disability and disease activity in RA patients. Fifty-seven female RA subjects and 20 age–gender-matched controls were included in a cross-sectional evaluation. An assessment of clinical characteristics, grip strength, gait speed, and muscle mass was conducted. In RA subjects, disability was assessed using HAQ-DI and active disease using the DAS28-ESR. Follistatin levels were measured by ELISA. We compared (a) RA + functional disability and (b) RA + preserved physical function. Serum follistatin levels were increased in RA subjects compared to controls (175 ± 119 vs. 133 ± 47; p = 0.030). Follistatin levels correlated with deteriorated physical function levels (r = 0.491; p < 0.001) and severe activity (r = 0.344; p = 0.009). The RA + functional disability group, as compared to the RA + preserved physical function group, had higher serum follistatin levels (218 ± 159 vs. 141 ± 59; p = 0.030), lower grip strength (7.9 ± 4.6 vs. 14.5 ± 5.1; p < 0.001), reduced gait speed (0.77 ± 0.20 vs. 0.92 ± 0.20; p = 0.010), as well as higher proportions of tender joints ≥4 (48% vs. 16%; p = 0.008), and higher disease activity scores (3.8 ± 1.5 vs. 2.8 ± 1.2; p = 0.008). We concluded that higher follistatin levels are associated with physical functional impairment and the severity of disease activity in women with RA. Future studies are required to evaluate whether these follistatin levels can be related to other outcomes such as labor disability, hospitalization, and falls. Full article
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15 pages, 1226 KB  
Article
Functional Textile Socks in Rheumatoid Arthritis or Psoriatic Arthritis: A Randomized Controlled Study
by Kirkke Reisberg, Kristiine Hõrrak, Aile Tamm, Margarita Kõrver, Liina Animägi and Jonete Visnapuu
Textiles 2025, 5(3), 30; https://doi.org/10.3390/textiles5030030 - 31 Jul 2025
Cited by 2 | Viewed by 1857
Abstract
There is limited knowledge about the benefits of functional textile in arthritis management. This study aimed to evaluate the effect of wearing functional socks in patients with rheumatoid or psoriatic arthritis. Patients were randomized into an experimental group (n = 23) and [...] Read more.
There is limited knowledge about the benefits of functional textile in arthritis management. This study aimed to evaluate the effect of wearing functional socks in patients with rheumatoid or psoriatic arthritis. Patients were randomized into an experimental group (n = 23) and control group (n = 18). The intervention involved wearing functional textile socks for 12 weeks. Sock composition was analyzed using X-ray fluorescence spectrometry and scanning electron microscopy. Outcome measures included the Numeric Rating Scale, Health Assessment Questionnaire–Disability Index (HAQ-DI), and RAND-36 (Estonian version). At week 12, the experimental group showed significantly lower metatarsophalangeal and toe joint pain (p = 0.001), stiffness (p = 0.005), and ankle stiffness (p = 0.017) scores than the control group. Improvements were also observed in HAQ-DI reaching (p = 0.035) and activity (p = 0.028) scores. RAND-36 scores were higher in physical functioning (p = 0.013), social functioning (p = 0.024), and bodily pain (p = 0.006). Role limitations due to physical problems improved in the experimental group but worsened in the control group (p = 0.029). In conclusion, wearing functional socks led to some statistically significant improvements in foot and ankle pain and stiffness, physical function, and health-related quality of life. However, the effect sizes were small, and the clinical relevance of these findings should be interpreted with caution. Full article
(This article belongs to the Special Issue Advances of Medical Textiles: 2nd Edition)
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13 pages, 239 KB  
Article
Genetic Variants of the ATIC Gene and Therapeutic Response to Methotrexate in Patients with Rheumatoid Arthritis
by Sergio Gabriel Gallardo-Moya, Laura Gonzalez-Lopez, Betsabe Contreras-Haro, Mario Alberto Mireles-Ramirez, Alejandra Villagomez-Vega, María Cristina Morán-Moguel, Miriam Méndez-Del Villar, María Luisa Vazquez-Villegas, Jorge Ivan Gamez-Nava and Ana Miriam Saldaña-Cruz
Int. J. Mol. Sci. 2025, 26(9), 4013; https://doi.org/10.3390/ijms26094013 - 24 Apr 2025
Viewed by 1806
Abstract
Methotrexate (MTX) is the conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) recommended as the first-choice anti-rheumatic drug for rheumatoid arthritis (RA). However, responses to MTX may be influenced by genetic variants. We aim to evaluate the association of the rs2372536, rs4673990, and rs4673993 genetic [...] Read more.
Methotrexate (MTX) is the conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) recommended as the first-choice anti-rheumatic drug for rheumatoid arthritis (RA). However, responses to MTX may be influenced by genetic variants. We aim to evaluate the association of the rs2372536, rs4673990, and rs4673993 genetic variants of the ATIC gene with therapeutic failure of MTX in patients with RA. A case–control study was performed. Disease activity was measured using the disease activity score based on erythrocyte sedimentation rate (DAS28-ESR). RA patients were classified into two groups: (a) responders (DAS28-ESR ≤ 3.2), which is the group of patients who did respond to methotrexate, and (b) non-responders (DAS28-ESR > 3.2), which is the group of patients who did not respond to methotrexate. Serum levels of the 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) enzyme and Interleukin-6 (IL-6) were quantified using an enzyme-linked immunosorbent assay (ELISA). Genotyping of ATIC genetic variants was performed with quantitative polymerase chain reaction (qPCR) using TaqMan probes. A total of 260 patients with RA were included. In total, 142 (54.6%) were non-responders to MTX. IL-6 levels were increased in the non-responder group (p = 0.002), while no statistical differences were observed in the AICAR levels. The variables associated with non-response were higher HAQ-Di, weekly MTX dose, glucocorticoid use, erythrocyte sedimentation rate, and carriers of the polymorphic homozygous variant of rs4673993 (OR = 4.5, 95% CI: 1.04–19.34; p = 0.04). The use of sulfazaline offered protective effects. Our findings indicate that the polymorphism rs4673993 gene variant of the AICAR protein may significantly influence MTX resistance. Therefore, these results support the importance of the pathway generating extracellular adenosine and its effects on promoting the immune regulation for the mechanism of MTX therapy of RA. Full article
(This article belongs to the Special Issue Rheumatoid Arthritis: From Molecular Basis to Therapies)
12 pages, 746 KB  
Article
Causes of Sleep Disturbance in Early ASAS Spondyloarthritis: A Retrospective Long-Term Experience
by Francesca Bandinelli, Andrea Delle Sedie, Ilenia Mallia, Ilaria Mauro, Nikita Pecani, Linda Carli, Lorenzo Esti, Marco Di Carlo, Marina Carotti and Fausto Salaffi
J. Pers. Med. 2025, 15(1), 31; https://doi.org/10.3390/jpm15010031 - 17 Jan 2025
Cited by 1 | Viewed by 2357
Abstract
Introduction: Sleep disturbance (SD) in the second half of the night due to inflammatory pain was included in the 2009 ASAS classification criteria of Spondyloarthritis (SpA), even though its definition is uncertain. Aim: We aimed to investigate SD in early-SpA (e-SpA) patients at [...] Read more.
Introduction: Sleep disturbance (SD) in the second half of the night due to inflammatory pain was included in the 2009 ASAS classification criteria of Spondyloarthritis (SpA), even though its definition is uncertain. Aim: We aimed to investigate SD in early-SpA (e-SpA) patients at T1 (2010–2013), comparing them to long-term SpA (l-SpA) patients at T2 (2023–2024) after at least 10 years of follow-up. Methods: At T1, in e-SpA and l-SpA cases, SD, classified as “difficulty in initiating sleep” (DIS), “difficulty in maintaining sleep” (DMS) and “early awakening” (EA), was compared to clinical parameters (ASDAS-CRP, BASDAI, m-HAQ-S, BASMI, MASES, 68/66 joint count, tenderness of sacroiliac joints, fatigue [FACIT] and HADS for anxiety [A] and depression [D]). At T2, e-SpA patients were re-evaluated using the Pittsburgh Sleep Quality Index (PSQI). Results: At T1, 45% of 166 SpA patients had SD; in e-SpA patients (60), SD correlated with sacroiliac pain (DMS) BASDAI, FACIT and HADS-D (EA); in l-SpA patients (106), it correlated with HADS-A (DIS), BASDAI and FACIT (DMS). At T2, e-SpA patients showed a high PSQI in 51.5% of cases, correlated with T2-ASDAS-CRP and T2-BASDAI. Moreover, T1-ASDAS-CRP was predictive of T2-PSQI. Conclusions: SD is more specific for inflammatory pain in e-SpA and might be influenced by disease activity also in long-term disease. Full article
(This article belongs to the Section Personalized Therapy in Clinical Medicine)
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11 pages, 288 KB  
Communication
Effective Assessment of Rheumatoid Arthritis Disease Activity and Outcomes Using Monocyte Chemotactic Protein-1 (MCP-1) and Disease Activity Score 28-MCP-1
by Ping-Han Tsai and Lieh-Bang Liou
Int. J. Mol. Sci. 2024, 25(21), 11374; https://doi.org/10.3390/ijms252111374 - 23 Oct 2024
Cited by 4 | Viewed by 1953
Abstract
The effectiveness of monocyte chemotactic protein-1 (MCP-1) and Disease Activity Score 28 (DAS28)-MCP-1 (DAS28-MCP-1) in assessing rheumatoid arthritis (RA) disease activity is unclear, although some studies have demonstrated their potential usefulness. The present study investigated relationships between MCP-1 and different DAS28 measures, the [...] Read more.
The effectiveness of monocyte chemotactic protein-1 (MCP-1) and Disease Activity Score 28 (DAS28)-MCP-1 (DAS28-MCP-1) in assessing rheumatoid arthritis (RA) disease activity is unclear, although some studies have demonstrated their potential usefulness. The present study investigated relationships between MCP-1 and different DAS28 measures, the occurrence of residual swollen joints in different DAS28 remission statuses, changes in medication dosage in relation to the 2005 modified American Rheumatism Association and 2011 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) remission definitions, and the correlations between different DAS28-related scores and Health Assessment Questionnaire Disability Index (HAQ-DI) scores in two RA patient cohorts. The results revealed that the MCP-1 level was correlated with five disease activity measures (DAS28-erythrocyte sedimentation rate [DAS28-ESR], DAS28-C-reactive protein [CRP], Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and DAS28-MCP-1) in multivariable regression analysis (all p < 0.05; ESR, CRP, and MCP-1 as independent variables). However, ESR was not significantly associated with SDAI and CDAI scores (p = 0.343 and 0.323, respectively). Residual swollen joints were more frequently observed in patients who met the DAS28-ESR remission criteria (<2.6) compared with those meeting the other four remission criteria, with a difference ranging from 71% to 94%. Among patients meeting the DAS28-ESR remission criteria (<2.6), medication changes (dose increase by ≥30% or new medications prescribed) were less frequent in those who also met the 2011 ACR/EULAR remission criteria than in those who did not meet them (p = 0.006). Moreover, the correlation coefficients for the relationship between DAS28-ESR and HAQ-DI scores were the lowest among the five disease activity measures. In conclusion, MCP-1 and DAS28-MCP-1 are effective in assessing RA disease activity, with less residual joint swelling and less frequent medication increases observed in the DAS28-MCP-1 remission < 2.2 subgroup. Full article
(This article belongs to the Special Issue Molecular Insights in Rheumatoid Arthritis)
15 pages, 958 KB  
Article
Predictors of Remission or Combined Remission and Low Disease Activity in Rheumatoid Arthritis Patients in Taiwan: A Prospective Cohort Study
by Ping-Han Tsai, Yao-Fan Fang, Yen-Fu Chen, Chih-Chieh Chen, Wen-Yu Chiang, Che-Tzu Chang, Yun-Ju Huang and Lieh-Bang Liou
J. Clin. Med. 2024, 13(9), 2521; https://doi.org/10.3390/jcm13092521 - 25 Apr 2024
Cited by 3 | Viewed by 2464
Abstract
Objectives: This study aimed to identify predictors of remission or low disease activity (LDA) in patients with rheumatoid arthritis (RA) and low-ultrasound inflammation. Methods: A total of 80 patients with RA who fulfilled the 1987 ACR criteria for RA with a [...] Read more.
Objectives: This study aimed to identify predictors of remission or low disease activity (LDA) in patients with rheumatoid arthritis (RA) and low-ultrasound inflammation. Methods: A total of 80 patients with RA who fulfilled the 1987 ACR criteria for RA with a disease activity score of 28 joints (DAS28) > 3.2 were recruited. Over 1 year of therapy, we conducted blood tests every 6 months to examine erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), neuraminidase 3 (Neu3), and α-2,3-sialyltrasnferse I (ST3Gal-1) levels in B cells and monocytes. Additionally, we evaluated physical function by using the Health Assessment Questionnaire–Disability Index (HAQ-DI). Data on demographic and clinical parameters were collected, and musculoskeletal ultrasonography was performed twice a year on 12 specific joints to assess synovial changes. One year later, we compared all collected data and laboratory or ultrasound results between patients achieving remission or LDA and those who did not in order to determine the predictors. Results: Age, the presence or absence of rheumatoid factor, and the number of conventional disease-modifying anti-rheumatic drugs used were not correlated with remission or LDA for DAS28 or Simplified Disease Activity Index formulas. However, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores were associated with a higher likelihood of achieving remission or LDA for DAS28-ESR. Negative anticyclic citrullinated peptide (CCP) and low HAQ-DI scores were predictors of remission or LDA for DAS28-MCP-1. Interestingly, having less than two comorbidities is a good predictor of a combined remission/low disease activity state for SDAI and DAS28-MCP-1. Furthermore, Neu3 and ST3Gal-1 levels and ST3Gal-1/Neu3 ratios in B cells and monocytes had no significant correlation with total ultrasound scores. Nevertheless, monocyte ST3Gal-1 and Neu3 correlated significantly with DAS28-ESR >5.1 and DAS-MCP-1 >4.8 (both categories belong to high disease activity), respectively (rho = 0.609 with p = 0.012, and rho = 0.727 with p = 0.011, respectively). Monocyte ST3Gal-1/Neu3 ratios connected with DAS28-ESR >5.1 and 3.3 < SDAI ≦ 11 (low disease activity), respectively (rho = 0.662 with p = 0.005, and rho = 0.342 with p = 0.048, respectively). Conclusions: In patients with RA in Taiwan, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores are predictors of remission or LDA for DAS28-ESR, which differ from the predictors for DAS28-MCP-1. Moreover, monocyte ST3Gal-1, Neu3, and their ratios correlated with different disease activity categories of DAS28-ESR, DAS28-MCP-1, and SDAI scores. Full article
(This article belongs to the Special Issue Clinical Updates on Rheumatoid Arthritis)
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13 pages, 261 KB  
Article
Real-Life Comparison of Four JAK Inhibitors in Rheumatoid Arthritis (ELECTRA-i Study)
by Maurizio Benucci, Francesca Li Gobbi, Arianna Damiani, Edda Russo, Serena Guiducci, Mariangela Manfredi, Barbara Lari, Valentina Grossi and Maria Infantino
J. Clin. Med. 2024, 13(6), 1821; https://doi.org/10.3390/jcm13061821 - 21 Mar 2024
Cited by 11 | Viewed by 11025
Abstract
Background: Real-world evidence of the efficacy and adverse events of JAK inhibitor treatment (Tofacitinib, Baricitinib, Upadacitinib, and Filgotinib) in rheumatoid arthritis is still limited. Methods: We studied 115 patients from the Rheumatology Unit of S. Giovanni di Dio Hospital affected by D2T-RA, according [...] Read more.
Background: Real-world evidence of the efficacy and adverse events of JAK inhibitor treatment (Tofacitinib, Baricitinib, Upadacitinib, and Filgotinib) in rheumatoid arthritis is still limited. Methods: We studied 115 patients from the Rheumatology Unit of S. Giovanni di Dio Hospital affected by D2T-RA, according to the 2010 EULAR criteria. Out of the 115 patients, 17 had been treated with Baricitinib 8 mg/daily, 32 with Filgotinib 200 mg/daily, 21 with Tofacitinib 10 mg/daily, and 45 with Upadacitinib 15 mg/daily. We evaluated the clinical response after 3, 6, and 12 months of treatment and the follow-up from September 2022 to September 2023. All patients were evaluated according to the number of tender joints (NTJs), number of swollen joints (NSJs), visual analog scale (VAS), global assessment (GA), health assessment questionnaire (HAQ), Disease Activity Score (DAS28), and CDAI. Furthermore, laboratory parameters of efficacy and tolerability were evaluated. Results: All treatments demonstrated a statistically significant decrease in the DAS28 and CDAI scores, tender and swollen joint counts, VAS, HAQ, and patient global assessment (PGA) after 3, 6, and 12 months of treatment. All treatments showed similar behavior, and statistically significant decreases in circulating calprotectin, TNFα, and IL-6 were observed for all drugs after 12 months of treatment. In addition, soluble urokinase plasminogen activator receptor (suPAR) values showed significant differences at baseline and after 12 months of treatment for Filgotinib: 4.87 ± 4.53 vs. 3.61 ± 0.9 (0.009) and Upadacitinib: 6.64 ± 7.12 vs. 4.06 ± 3.61 (0.0003), while no statistically significant differences were found for Baricitinib: 3.4 ± 0.1 vs. 3.78 ± 0.1 and Tofacitinib: 3.95 ± 1.77 vs. 2.58 ± 0.1. The TC/HDL-C ratio (atherogenic index) showed significant differences when comparing Baricitinib vs. Filgotinib (0.0012), Filgotinib vs. Tofacitinib (0.0095), and Filgotinib vs. Upadacitinib (0.0001); furthermore, the LDL-C/HDL-C ratio in the Filgotinib group did not change (2.37 ± 0.45 vs. 2.35 ± 2.13 (NS)) after 12 months of treatment. Venous Thrombotic Events (VTEs) and major adverse cardiovascular events (MACEs) accounted for 1% of adverse events after treatment with Baricitinib. Herpes zoster reactivation accounted for 1% of adverse events after treatment with Filgotinib and Tofacitinib, while non-melanoma skin cancer (NMSC) accounted for 1% of adverse events after Upadacitinib treatment. Conclusions: Our real-world data from patients with RA show differences in some laboratory parameters and in the impact of lipid metabolism in JAK inhibitor treatment. Full article
15 pages, 391 KB  
Article
STAT4 Gene Variant rs7574865 Is Associated with Rheumatoid Arthritis Activity and Anti-CCP Levels in the Western but Not in the Southern Population of Mexico
by Karla Mayela Bravo-Villagra, José Francisco Muñoz-Valle, Christian Johana Baños-Hernández, Sergio Cerpa-Cruz, José Eduardo Navarro-Zarza, Isela Parra-Rojas, José Alonso Aguilar-Velázquez, Samuel García-Arellano and Andres López-Quintero
Genes 2024, 15(2), 241; https://doi.org/10.3390/genes15020241 - 14 Feb 2024
Cited by 15 | Viewed by 4943
Abstract
Rheumatoid Arthritis (RA) is a multifactorial autoimmune disease. Currently, several genes play an important role in the development of the disease. The objective was to evaluate the association of the STAT4 rs7574865 and rs897200 gene variants with RA susceptibility, DAS28, RF, and anti-CCP in [...] Read more.
Rheumatoid Arthritis (RA) is a multifactorial autoimmune disease. Currently, several genes play an important role in the development of the disease. The objective was to evaluate the association of the STAT4 rs7574865 and rs897200 gene variants with RA susceptibility, DAS28, RF, and anti-CCP in Western and Southern Mexico populations. Genotyping was performed on 476 samples (cases = 240; controls = 236) using the Taqman® system and qPCR probes. Disease activity was assessed using DAS28 and HAQ DI. CRP, ESR, RF, and anti-CCP were determined for clinical assessment. Our study showed there is a statistically significant association with susceptibility to RA for the rs7574865 variant in the Western population for the GT and TT genotypes. The same genotypes also showed a moderate-to-high activity according to DAS28 and positive anti-CCP compared to the control group. This association was not found in the Southern population. This work confirms the association of the rs7574865 variant with RA, as well as a moderate-to-high activity and positive anti-CCP in the Western population but not in the Southern population. No association of the rs897200 variant was found in any of the studied populations. Full article
(This article belongs to the Special Issue Autoimmune Disease Genetics Volume II)
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12 pages, 1090 KB  
Article
The Extent and Nature of Functional Limitations According to the Health Assessment Questionnaire Disability Index in Patients with Rheumatoid Arthritis and Severe Functional Disability
by Max M. H. Teuwen, Maria A. T. van Wissen, Wilfred F. Peter, Dirkjan van Schaardenburg, Cornelia H. M. van den Ende, Maaike G. J. Gademan and Salima F. E. van Weely
J. Clin. Med. 2024, 13(2), 379; https://doi.org/10.3390/jcm13020379 - 10 Jan 2024
Cited by 8 | Viewed by 3554
Abstract
Background: For a subgroup of people with rheumatoid arthritis (RA) and severe disability, insight into their limitations is crucial for adequate treatment. Aim: To describe the extent and nature of functional limitations in people with RA and severe disability and to explore the [...] Read more.
Background: For a subgroup of people with rheumatoid arthritis (RA) and severe disability, insight into their limitations is crucial for adequate treatment. Aim: To describe the extent and nature of functional limitations in people with RA and severe disability and to explore the associations of the extent of the functional limitations with patient characteristics, disease characteristics, and outcome measures. Methods: Baseline data of 215 participants in an RCT on the (cost-)effectiveness of longstanding physiotherapy were used. Functional limitations were assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI). The total HAQ-DI including eight domain scores were calculated. Associations between high HAQ-DI scores (≥2, yes/no) and other variables were examined using the Student’s t-test or Chi-squared test where appropriate. Results: The participants (90% women, age 58.8 ± 12.8 years) had a mean HAQ-DI score of 1.7 ± 0.5. The majority (56%) showed a moderate-to-severe disability in all domains. Higher HAQ-DI scores seemed to be associated with advanced age, longer disease duration, unemployment, joint replacements, and outcomes for daily functioning and physical quality of life, but not with measures of disease activity. Conclusions: Our findings indicate that a comprehensive assessment of all areas of daily activities in this subgroup is necessary in order to provide appropriate (non-)pharmacological care. Full article
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12 pages, 373 KB  
Article
Validation of the Portuguese Version of the Scleroderma Health Assessment Questionnaire
by Inês Genrinho, Pedro L. Ferreira, Tânia Santiago, Adriana Carones, Carolina Mazeda, Anabela Barcelos, Tiago Beirão, Flávio Costa, Inês Santos, Maura Couto, Maria Rato, Georgina Terroso and Paulo Monteiro
Int. J. Environ. Res. Public Health 2023, 20(22), 7062; https://doi.org/10.3390/ijerph20227062 - 14 Nov 2023
Cited by 5 | Viewed by 2664
Abstract
The Health Assessment Questionnaire Disability Index (HAQ-DI) was completed with five visual analog scales to assess systemic sclerosis (SSc) called Scleroderma HAQ (SHAQ). We performed a validation of the European Portuguese version of SHAQ for patients with SSc. Patients with different forms of [...] Read more.
The Health Assessment Questionnaire Disability Index (HAQ-DI) was completed with five visual analog scales to assess systemic sclerosis (SSc) called Scleroderma HAQ (SHAQ). We performed a validation of the European Portuguese version of SHAQ for patients with SSc. Patients with different forms of SSc from five Hospital Centers were invited. The reliability of the Portuguese SHAQ was evaluated by internal consistency and by test–retest reliability. Content validity was checked by two rheumatologists and by a panel of patients. Construct validity was assessed by structural validity and by known-groups hypothesis tests. Criterion validity was addressed with selected dimensions from the UCLA GIT 2.0, the SF-36v2, and the EuroQoL EQ-5D-5L. A total of 102 SSc patients agreed to participate, 31 of which answered to the retest. HAQ-DI demonstrated high internal consistency reliability (α = 0.866) and SHAQ also showed high test–retest reliability (ICC 0.61–0.95). We evidenced the unidimensionality of all VASs. HAQ-DI scores were worse in males, patients older than 65 years, and individuals with a diffuse form of SSc. Criterion validity was mainly evidenced through the correlation between the HAQ-DI and SF-36v2 physical summary measure (r = −0.688) and EQ-5D-5L index score (r = −0.723). Likewise, the SHAQ overall disease severity VAS was also correlated with SF-36v2 physical summary measure (r = −0.628). Mental score correlations were smaller. With the exception of the Raynaud’s VAS, all the other VASs correlated well with similar clinical variables. This paper provides evidence to demonstrate how reliable and valid the European Portuguese version of SHAQ is, to be used in SSc patients to assess the clinical severity under the perspective of patients. Full article
11 pages, 296 KB  
Article
Regular Exercise Improved Fatigue and Musculoskeletal Pain in Young Adult Psoriatic Patients without Psoriatic Arthritis
by Antonio J. Diaz, Miguel A. Rosety, Jose C. Armario, Manuel J. Bandez, Natalia Garcia-Gomez, Eduardo Sanchez-Sanchez, Jara Diaz, Cristina Castejon-Riber, Marco Bernardi, Manuel Rosety-Rodriguez M, Francisco J. Ordonez and Ignacio Rosety
Nutrients 2023, 15(21), 4563; https://doi.org/10.3390/nu15214563 - 27 Oct 2023
Cited by 5 | Viewed by 4090
Abstract
Fatigue and musculoskeletal pain are also frequent in patients with psoriasis (PsO) without arthritis (PsA). The current study aimed to assess the impact of an intervention program based on aerobic training to reduce fatigue and musculoskeletal pain in patients with PsO without PsA. [...] Read more.
Fatigue and musculoskeletal pain are also frequent in patients with psoriasis (PsO) without arthritis (PsA). The current study aimed to assess the impact of an intervention program based on aerobic training to reduce fatigue and musculoskeletal pain in patients with PsO without PsA. A total of 118 male patients with PsO volunteered in the current interventional study and were randomly allocated to the experimental (n = 59) or control group (n = 59). The intervention consisted of a 16-week aerobic training program on a treadmill, three sessions per week, consisting of a warm-up, 35–50 min treadmill exercise (increasing 5 min/4 weeks) at a work intensity of 50–65% of peak heart-rate (increasing 5%/4 weeks), and cooling-down. The functional assessment of chronic illness therapy fatigue scale (FACIT-Fatigue), health assessment questionnaire disability index (HAQ-DI), and visual analog scale (VAS) were compared pre and post intervention. Nutritional intake, maximal aerobic power, lipid profile, serum markers of muscle damage, and body composition were also assessed. When compared to baseline, FACIT-Fatigue, HAQ-DI, and VAS scores were significantly improved without increasing markers of muscle damage. Fat mass percentage, lipid profile, and maximal oxygen consumption were also improved. In conclusion, a 16-week aerobic training program at moderate intensity was safe, well tolerated, and effective in psoriatic patients without PsA. Long-term follow-up studies are required to examine whether these promising results may improve clinical outcomes. Full article
(This article belongs to the Special Issue Nutrition, Physical Activity and Musculoskeletal Health)
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